Clinical outcomes of extensive-stage small cell lung cancer patients treated with thoracic radiotherapy at different times and fractionations

Abstract

Abstract Objective The purpose of this study was to assess whether thoracic radiotherapy (TRT) combined with chemotherapy (CHT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC), to explore practice patterns for the radiation time and dose/fractionation and to identify prognostic factors for patients who would benefit from CHT/TRT. Methods A total of 492 ES-SCLC patients were included from January 2010 to March 2019, 244 of whom received CHT/TRT. Propensity score matching was performed to minimize bias between the CHT/TRT and CHT-alone groups. Patients in the CHT/TRT group were categorized into four subgroups based on the number of induction CHT cycles. For effective dose fractionation calculations, we introduced the time-adjusted biological effective dose (tBED). Categorical variables were analysed with chi-square tests and Fisher’s exact tests. Kaplan–Meier curves were generated to estimate survival rates using the R-project. Multivariate prognostic analysis was performed with Cox proportional hazards models. Results Patients who received CHT/TRT experienced improved overall survival (OS) (18.1 vs 10.8 months), progression-free survival (PFS) (9.3 vs 6.0 months) and local recurrence-free survival (LRFS) (12.0 vs 6.6 months) before matching, with similar results after matching. In the CHT/TRT group, the median LRFS times for the groups based on the radiation time were 12.7, 12.0, 12.0, and 9.0 months, respectively. Early TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.0 vs 7.7 months, respectively, p = 0.091) but not OS (median 17.6 vs 19.5 vs 17.2 vs 19.0 months, respectively, p = 0.622). Notably, patients who received TRT within 6 cycles of CHT experienced prolonged LRFS (p = 0.001). Regarding the radiation dose, patients in the high-dose group (tBED > 50 Gy) who achieved complete response and partial response (CR and PR) to systemic therapy had relatively short OS (median 27.1 vs 22.7, p = 0.026) and PFS (median 11.4 vs 11.2, p = 0.032), but the abovementioned results were not obtained after the exclusion of patients who received hyperfractionated radiotherapy (all p > 0.05). Conclusion CHT/TRT could improve survival for ES-SCLC patients. TRT performed within 6 cycles of CHT and hyperfractionated radiotherapy (45 Gy in 30 fractions) may be a feasible treatment scheme for ES-SCLC patients.